Introduction

Malaria is a disease caused by Plasmodium parasites 

-it is transmitted by the bite of infected female anopheline mosquitoes

-it is uncommon in temperate climates, but still common in tropical and subtropical countries 

-it is the most significant disease acquired through international travel to the tropics

–approximately half of the world’s population are at risk for malarial infection each year

-Five species of the genus Plasmodium infect humans: Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, Plasmodium falciparum, and Plasmodium knowlesi

-While Plasmodium falciparum is the most common cause of serious malaria, P vivax and P knowlesi can also cause severe and fatal infections

-Plasmodium falciparum is also responsible for cerebral malaria 

-Severe malaria is a medical emergency and requires hospitalization 

Pathophysiology 

Step 1: Infected female Anopheles mosquito bites, infects humans: Sporozoites are released from the mosquito into the human bloodstream 

Step 2: Liver stages: Sporozoites migrate to the liver and start multiplication through asexual reproduction within hepatocytes. The daughter cells are called merozoites. Hepatocytes rupture and release merozoites into the circulation.  

Step 3: Red blood cell stages: Merozoites enter the bloodstream and invade red blood cells. A merozoite enters an erythrocyte, multiples within and forms a schizont. 

Step 4: Invasion of the body: A schizont ruptures to release merozoites which releases pyrogens into the bloodstream causing malaria. Thus, symptomatic malaria is caused only by the erythrocytic stage of infection. 

Step 5: Infection of the mosquito: A portion of the merozoites develop into sexual forms (gametocytes). Feeding on its human host, Anopheles mosquito swallows male and female gametocytes, which undergo sexual reproduction in its gut. They produce sporozoites which travel to the salivary glands waiting to be injected into the next innocent human victim. 

Symptoms & Signs: Fever,chills, myalgia, malaise, headache, cough, chest pain, abdominal pain, nausea, vomiting, diarrhea, arthralgia, tachycardia, tachypnea, and splenomegaly

Fever may follow regular cycles 48-hour (P vivax and P ovale) or 72-hour (P malariae) cycles

Severe complications: Anemia, jaundice, renal failure, metabolic acidosis (pH <7.35), hypoglycemia, shock, disseminated intravascular coagulopathy, pulmonary edema, acute respiratory distress syndrome, impaired consciousness, seizures

Diagnosis 

Thick and thin blood films, Rapid diagnostic tests, PCR based tests 

Treatment 

-no antimalarial drug kills sporozoites, so it is not truly possible to prevent infection using drugs 

-Drugs can prevent symptomatic malaria by inhibiting asexual merozoite production in the hepatocytes 

Artemisinin and derivatives: Artemisinin-based combination therapies (ACTs) achieve the fastest clearance of parasites from the blood; According to the WHO, IV artesunate is the drug of choice for severe malaria, effective against  drug-resistant P falciparum;  Co-Artem (Artemether/ Lumefantrine) may cause hearing loss 

Atovaquone/proguanil: useful in malaria chemoprophylaxis, it acts at both the liver and the blood stage; can cause oral aphthous ulcers; can enhance warfarin anticoagulation; Contraindications: pregnancy, severe renal insufficiency  

Chloroquine: Chloroquine is the drug of choice for the treatment of sensitive non-falciparum and sensitive falciparum malaria; causes generalized pruritis in black people; Contraindications: Psoriasis, epilepsy 

Mefloquine: first-line drug (taken weekly) given for prophylaxis in all geographical areas with chloroquine resistance; most frequent side effects are vivid dreams, mood changes, insomnia; Contraindications: serious psychiatric disease, seizure disorder 

Primaquine: effective against the liver stages, blood stages and gametocytes; Contraindications: pregnancy, G6PD deficiency, all individuals should have G6PD screening prior to treatment

Quinine: Parenteral quinine is used for severe malaria when parenteral artesunate is not available; it is cardiotoxic; can cause Quinine-induced hyperinsulinemic hypoglycemia; blood glucose concentrations should be monitored; can also cause  hypotension, thrombocytopenia, erythematous rash, increased uterine contractions in pregnant women leading to miscarriage 

Quinidine: a diastereomer of quinine and is more toxic; can cause hypotension and QT prolongation; requires electrocardiographic monitoring 

Doxycycline: effective as chemoprophylaxis and treatment; should be taken daily; Side-effects include photosensitivity, gastrointestinal upset, esophageal ulceration. Contraindications: pregnancy, breast-feeding, and children less than 8 years of age

Clindamycin:  is less effective than doxycycline or atovaquone/proguanil; can be used when other drugs cannot be used (pregnant women, young children)

Pyrimethamine-sulfadoxine: it inhibits folate synthesis in the parasite; of little use due to drug resistance